Studies on the Chemistry of Blood Coagulation Ii. on the Inhibition of Blood Clotting by Substances of High Molecular Weight* by Erwin Chargaff,

The discovery in liver of the anticoagulant heparin by Howell and Holt (1) probably marks the greatest progress in the theory of blood clotting since the times of Schmidt and Hammarsten. The fact that representatives of both classes of substances having antagonistic effects in blood clotting, viz. the activators and inhibitors, occur in animal tissue may form the basis for the assumption that there normally exists in the body an equilibrium between these substances, which is disturbed in certain pathological cases (e.g. thrombosis, hemophilia, etc.). Howell (2) was the first to draw attention to the fact that heparin was probably formed of a complex containing uranic acids, calcium, and sulfuric acid. The importance of the -SO,H group for the inhibition of blood clotting was emphasized by Demole and Reinert (3) and by Fischer (4). The high ash content of heparin has been pointed out by almost all workers on this subject. Jorpes (5) has recently reported the isolation from heparin, prepared from ox and horse liver according to the method of Charles and Scott (6), of a substance which he considers to be a chondroitintrisulfuric acid. According to Schmitz (7), however, heparin prepared by the procedure of Schmitz and Fischer (8) does not contain sulfuric acid. While the work here described was in progress, Bergstrom (9) reported on a number of polysaccharide sulfuric acids with heparin activity.